Study guide for Biol 416

Chapter 1 Genetics of Cancer

Know the following and any other genetic terminology I used in class (look it
up! and crystallize it) and be able to describe:
Pleiotropy Ability of a gene or protein to concomitantly evoke a series of
distinct downstream responses within a cell or organism
Polymorphism, allele A variant germ-line allele that does not appear to
be associated with any pathology and, by implication, is a reflection of
normal intraspecies genetic variability. An allele is one alternative among
different versinos of a gene that may be defined by the phenotype that it
creates, by the protein that it specifies, or by its nucleotide sequence.
Epigenetics and methylation Epigenetics is the study of heritable
changes in gene expression that are not due to alteration in the primary DNA
sequence. Methylation is the addition of a methyl group to a substrate.
FISH analysis Fluorescent in situ hybridization. Technique developed in
1980s used to detect and localize the presence of specific DNA sequences on
chromosomes.
microRNA Endogenously synthesized RNA transcribed by RNA polymerase
II and processed into 21- to 23-nt-long ssRNA that interferes with translation
of an mRNA or causes its degradation, depending on the degree of
complementarity with the mRNA
Histone acetylation/deacetylation Process by which lysine residues
within the N-terminal tail protruding from the histone core of the nucleosome
are acetylated and decacetylated as part of gene regulation.
Transcription factors/promoters/enhancers Transcription factor is a
protein involved in regulating the transcription of a gene, often by
associating with sequences in the promoter region of the gene.
Gene activation/repression/constitutive expression Activators
enhance interaction between RNA polymerase and a particular promoter.
Repressors bind to the Operator, impeding RNA polymerases progress along
a strand of DNA. Constitutive genes are genes that are expressed regardless
of the cells surrounding environment.
Stem cells/pluripotency Pluripotency refers to stems cells that have an
ability to differentiate into any of the three germ layers (endoderm,
mesoderm, or ectoderm).
Drives and passenger genes A driver mutation is a mutation creating an
ellele that is advantageous for the cell that sustains it and results in clonal
expansion of progeny bearing this particular mutation. A passenger
mutation is a mutation that confers no selective advantage on a cell carrying
it but whose presence in a population of cells is increased because it resides
in the same genome as other mutant alleles that do indeed confer
advantage.

DNA transfection (calcium phosphate) Procedure of introducing DNA

into mammalian cells, often achieved by calcium phosphate coprecitpitation.
Point mutation (missense, nonsense, insertion, deletions,
frameshifts) A missense mutation results in a single nucleotide change
that results in a codon that codes for a different amino acid. A nonsense
mutation results in a premature stop codon. An insertion is the addition of
one or more nucleotide base pairs in a DNA sequence. A deletion is the
removal of one or more nucleotide base pairs in a DNA sequence. A
frameshift is caused by insertions or deletions that are not divisible by three,
thus the reading frame for the codons is shifted.
Cancer is said to be a disease of the somatic cell: explain the
genetic changes often seen in cancer cells, comparing and
contrasting the early tumor cell type with one that is highly
metastatic and leading to secondary tumors (later during
malignancy).
Tumors begin via uncontrolled cloning by a single cell. As the tumor grows, it
loses contact inhibition and moves towards hyperplasia, or accumulation of
excessive normal-appearing tissue. This leads to anaplasia, or cells that are
no longer differentiated. A malignant tumor will express severe dysplasia, in
which cells composing tissue are completely abnormal. Late in tumor
growth, tumors may lose anchorage dependence and metastasize, or have
cells break off from the primary tumor and form secondary tumors elsewhere
in the body.
Navigate a database and tell me about AKT, its mutations found in
cancer, its primary amino acid sequence (you can use OMIM, NCBI,
COSMIC, GENECARDS, ATLAS of GENETIC and CYTOGENETICS, etc.),
its map position and its role in signaling (CELL SIGNALLING
TECHNOLOGY).
AKT is also known as Protein Kinase B. It is a serine and threonine specific
protein kinase that plays a role in apoptosis, cell proliferation, and
transcription.
MSDVAIVKEGWLHKRGEYIKTWRPRYFLLKNDGTFIGYKERPQDVDQREAPLNNFSVAQC
QLMKTERPRPNTFIIRCLQWTTVIERTFHVETPEEREEWTTAIQTVADGLKKQEEEEMDF
RSGSPSDNSGAEEMEVSLAKPKHRVTMNEFEYLKLLGKGTFGKVILVKEKATGRYYAMKI
LKKEVIVAKDEVAHTLTENRVLQNSRHPFLTALKYSFQTHDRLCFVMEYANGGELFFHLS
RERVFSEDRARFYGAEIVSALDYLHSEKNVVYRDLKLENLMLDKDGHIKITDFGLCKEGI
KDGATMKTFCGTPEYLAPEVLEDNDYGRAVDWWGLGVVMYEMMCGRLPFYNQDHEKLFEL
ILMEEIRFPRTLGPEAKSLLSGLLKKDPKQRLGGGSEDAKEIMQHRFFAGIVWQHVYEKK
LSPPFKPQVTSETDTRYFDEEFTAQMITITPPDQDDSMECVDSERRPHFPQFSYSASGTA
Tumor cells are often found to have highly phosphorylated (highly active) AKT.
Map position:

Chapter 2 Pathohistology

Define the nature of cancer (unregulated growth, evasion/invasion,

i.e. metastases, secondary tumors, and the language of the
histologist/pathologist) Normal cells have growth pathways that are
highly regulated. In cancer cells, these pathways become unregulated for
some reason, leading to unregulated growth and the creation of a tumor.
Research showed that tumors were not the result of a pathogen invading the
body, but rather they derive from the normal tissue in which they are
discovered. Tumor cells are capable of moving within the body and
establishing new cancer cell colonies. The new settlements are termed
metastases, and are said to arise from a primary tumor.
Neoplasia (benign and malignant) Neoplasia is the state of cancerous
growth, benign and malignant tumors composed of cells have an abnormal
appearance and abnormal proliferation period.
Hyperplasia An accumulation of excessive numbers of normalappearing cells within a normal-appearing tissue. Also refers to increase in
the size of a tissue or organ due to increased cell number rather than
increased size of constituent cells.
Anaplasia having tissue and cellular architecture lacking the
differentiated characteristics of an identifiable tissue-of-origin.
Dysplasia A premalignant tissue composed of abnormally appearing
cells forming a tissue architecture that deviates from normal.
Metaplasia Replacement in a tissue belonging to cells of one
differentiation lineage by cells belonging to another lineage.
Hypertrophy (simply put, a cell that grows in size) An incrase
in the size of a tissue or organ due to increased sizes of component cells
rather than increased number of cells.
Carcinoma versus sarcoma versus hematological cancers versus
neuroectodermal Tumors Carcinoma is a cancer that develops from
epithelial cells (line the cavities and surfaces of structures of body). Sarcoma
tumors arise from mesenchymal cells (lymphatic and circulatory systems).
Hematological tumors arise from blood cells. Neuroectodermal tumor is a
tumor of the central of peripheral nervous system.
Tumorigenesis literally the creation of cancer.
Differentiation/dedifferentiation Differentiation is a process in which a
less specialized becomes more specialized. Dedifferentiation occurs when a
specialized cell becomes less specialized, often a sign of cancer.
Monoclonal nature of a tumor and how to prove this In a monoclonal
tumor, only a single cell is transformed from normal to cancerous behavior to
become the ancestor of the cells in a tumor mass. Monoclonality can be
proven in vivo via naturally occurring epigenetic marking events. The gene
for glucose-6-phosphate dehydrogenase (G6PD) is located on the X
chromosome, and more than 30% of African American women are
heterozygous at this locus. Through random X-inactivation, a cell will only
express one allele of the G6PD gene. Gel electrophoresis of a tumor mass

allows lineage tracing to prove that one cell is the ancestor of all the tumor
cells.
Carcinogen versus mutagen and the Ames test A carcinogen is an
agent that directly causes cancer. A mutagen is a physical or chemical agent
that increases the frequency of mutations. The Ames test is a test that uses
bacteria to see whether a chemical agent can cause mutagens in DNA of the
test organism.
Epithelial tissues are generally found to be the cell type giving rise
to malignant tumorswhy?
Epithelial tissues line of the cavities and surfaces of structures throughout
the body. Cancer among these tissue is referred to as carcinoma. The
primary function of epithelial cells is to protect the tissue underneath it from
toxins and pathogens. For this reason, epithelial tissue is often damaged in
some manner and in need of repair. Carcinomas are thought to arrive in a
large part due to a failure in proper DNA repair. A deficiency of DNA repair
allows DNA damages to accumulate, giving rise to error prone translation
synthesis.
As a pathologist, describe the cellular changes and events that
correspond to the transition of a normal cell to a malignant cell.
A normal cell has within it several regulatory features that prevent it from
turning into a cancer cell. The disruption of these regulatory pathways leads
to tumorigenesis. Continued phosphorylation of the Ras to Raf to Mek to Erk
pathway leads to continued cell proliferation. The tumor cells will lose
contact inhibition, or the proper signaling from the ECM to cease growing and
dividing. Tissue may develop hyperplasia, the excessive growth of normalappearing cells, or anaplasia, the excessive growth of cells that have lost
differentiation. As a tumor grows it becomes more malignant. It has the
potential to lose anchorage dependence, and thus metastasize and spread to
other areas of the body. This leads to metaplasia within the body, in which
tissue normally not found in an area of the body is found growing there.
Youve heard of nature versus nurture: apply this to malignant
transformation and the weight attributable to germline mutation
versus somatic mutation and the influence of environment.
A germline mutation is a mutation within the gametes of an individual.
These mutations can be passed onto other generations, and depending on
the type of mutation, be fatal. A somatic mutation occurs within the soma
cells of the body, it cannot be passed down to progeny. A majority of cancers
are somatic in nature. A carcinogen, an agent that directly causes cancer
such as radiation from gamma rays, can cause cancer. Mutagens may also
cause cancer. Point mutations may result in the disruption of a regulatory
pathway within the cell, leading to uncontrolled cell proliferation. A
pathogen such as a virus can also cause a mutation my inserting its own

genetic information into the host DNA and turning a proto-oncogene into an
oncogene.

Chapter 3 Tumor viruses

Describe the major types of viruses causing cancer, including
retroviruses, papilloma viruses, SV40 (T antigen), the herpes
viruses and the hepatitis viruses. A retrovirus is a virus that replicates
in the host cell via reverse transcriptase. The virus infects a cell, and once
inside uses its own reverse transcriptase enzyme to produce DNA from its
RNA. The integrase enzyme then incorporates the DNA into the hosts
genome, at which point the retroviral DNA is referred to as a provirus. If the
proviral DNA is placed in front of a proto-oncogene, the result could be
cancer. HPV (human papilloma virus) has oven 100 distinct types that infect
humans. Some cause benign lesions, while others lead to cancer. SV40 is a
simian virus that was discovered as a contaminate of the poliovirus vaccine
stock. SV40 T antigen is a protein derived from SV40. Since SV40 has a
relatively simple genome, it requires integration into host DNA in order to
proliferate. SV40 DNA replication is initiated by the binding of the large T
antigen to the origin region of the genome. SV40 T antigen is instrumental
in suppressing tumor suppressor protein p53, allowing the cell to enter S
phase and promote DNA replication. Due to the integration of the proviral
DNA, cell and viral DNA are replicated together, and SV40 T antigen persists
in daughter cells.
The general structure of a virus (capsid, external proteins that serve
as ligands for cellular receptors, what is meant by tropism, viral
genomes) The genetic information of a virus is protected by a coat of
protein called a capsid. Attachment refers to the specific binding between
viral capsid proteins and specific receptors on a cell surface. Specificity
determines the range of the virus. Tropism refers the way in which different
viruses have evolved to preferentially target specific host tissue. Viral
genomes are circular, as in polyomaviruses, or linear, as in adenoviruses.
Type of nucleic acid is irrelevant to shape of the genome.
The work of Peyton Rous Peyton Rous discovered the Rous Sarcoma
Virus in chickens. Rous took cells from a tumor on a chicken, and
transmitted the tumor by implanting small fragments of it into other birds of
the same breed. In a variation of the experiment, he found that grinding the
tissue and filtering it through sand resulted in the filtrate being able to
develop tumors on other chickens. These induced tumors could also be
homogenized to yield an infectious agent that could be transmitted to other
birds. This showed that the carcinogenic agent was a virus.
Avian Leukosis virus versus Rous Sarcoma Virus ALV becomes RSV
following insertion and altered repackaging via a longer RNA intermediate.
Integration, cDNA and the provirus Integration is the insertion of viral DNA
into host genome. cDNA is complementary DNA synthesized from mRNA by

reverse transcriptase. Provirus is a virus genome integrated in the DNA of

the host cell.
Transduction Process by which a gene is introduced into a cell, usually by
a vector such as a viral vector.
Episomal versus integrative expression of the viral genome
Episomal expression is expression of proteins and RNA by the virus.
Integrative expression occurs after viral DNA is integrated into the host
genome.
Insertional mutagenesis mutagenesis of DNA by the insertion of one or
more base pairs.
Life cycle of a retrovirus, its genes (gag, env, pol) Virus enters cell,
reverse transcriptase and integrase associate with viral RNA. (-) strand viral
DNA produced via reverse transcriptase, viral RNA removed, and (+) strand
viral DNA synthesized by reverse transcriptase. Viral dsDNA integrated into
host cell chromosome to form provirus. Transcription occurs via host cell
RNA polymerase II, new viral RNA produced. Viral RNA translated to produce
new viral proteins, viral proteins assemble with viral RNA genomes to form
progeny virions. Progency leave cell to initiate new infectious cycle. Gag,
group-specific antigen, codes for core structural proteins of retrovirus. Pol is
reverse transcriptase. Env is protein envelope.
Substractive hybridization (blue box sidebar 3.4, one of the few I
will require you to grasp) Bishop and Varmus used two RSV strains: a
wild type strain with v-src and a mutated strain that could replicated but had
lost v-src due to a deletion. Using reverse transcriptase, a DNA copy was
made of the wild-type sequence, yielding single-stranded cDNA. This was
hybridized to the RNA genome of the RSV deletion mutant that lacked src
sequences. The bulk of the cDNA fragments annealed to the mutant RSV
with the exception the cDNA segment derived from the v-src gene. The
ssDNA molecules that failed to form DNA-RNA hybrids resulted in src specific
probes. Because the intial reverse transriptino of the wilde-type RSV RNA
was carried out in the presence of radiolabeled deoxyribonucleoside
triphosphates, the src-specific sequences were also labeled with
radioisotopes. This made it possible to discover whether DNAs of interest
(such as DNAs from infected and uninfected cells) also carried src sequences
by determining if the src probe hybridized with the cellular DNA.
In vitro growth phenotypes correlating with tumor cell behavior
Anchorage independence The cell no longer needs to be bound to
a stable surface to grow.
Lack of contact inhibition Cell continues to grow despite being
crowded by other cells.
Foci A cluster of transformed cells growing amid a surrounding
monolayer of normal cells in culture.
Transformant A transformed cell.
Immortalization Process whereby a cell population normally having
limited replicative potential acquires ability to multiply indefinitely

Fetal calf serum and growth factors Growth factor is a protein

that is able to stimulate the growth and/or proliferation of a cell by binding to
a specific cell surface receptor displayed by that cell.
Src, everything about it that we went over in class, its mutation in
v-src, its
Structure, its regulation (inactive versus active), its functionSrc is a protein kinase (kinases add phosphates). C-src is a proto-oncogene.
SH3 is the proline binding domain, SH2 is the intramolecular phosphotyrosine
binding domain (negative control). SH1 is the kinase domain. SH2 and SH3
are part of a variety of kinases and are found across hundreds of proteins.
SH1 homology is less conserved.
Proto-oncogene versus oncogene An oncogene is a gene that has the
potential to cause cancer. A proto-oncogene is a normal gene that can
become an oncogene due to a mutation.
Temins conditional mutant (temperature sensitivity) Howard Temin
worked with RSV, transforming cells in vitro. Cells with normal morphology
were infected with RSV mutant and thus transformed. Transformed cells
were shifted to a higher temperature, during which the cells reverted back to
normal morphology. When temperature was lowered back to a permissive
state, and transformed morphology was once again seen. The loss of
transformed phenotype upon temperature up-shift demonstrated that the
continuous action of some temperature-sensitive viral protein was required in
order to maintain this phenotype. The reacquisition of the transformed
phenotype after temperature shift-down days later indicated that the viral
genome continued to persist in the cells at higher temperatures, despite
normal phenotype.
KINASES, composition of the phosphate group, the R side chains of SERINE,
THREONINE and TYROSINE
Transforming retroviruses have been so important for uncovering
oncogenes, and working in reverse, characterizing the protooncogenes from which they were derivedexplain their historical
and molecular significance (src, erb, etc.; take a look at Table 3.3).
Peyton Rous begin his work with tumor viruses early in the twentieth century.
Rous was able to show that serial passage of Rous Sarcoma Virus led to the
proliferation of cancer on chickens. RSV was a retrovirus, which is able to
replicate via reverse transcription. The study of other retroviruses such as
HPV and SV40 shed greater information into how RSV functioned. Once
inside a cell, the retrovirus is able to create cDNA via its own reverse
transcriptase protein. This DNA is then integrated as a provirus into the host
genome via integrase. The host treats the provirus as part of its own
genome and transcribes it along with the cells own genes. Speculating the
viral transforming functions of RSV took place upon a single gene,
researchers aimed to find it, nicknaming it src. What researchers found is
that all chickens already contain within them a src sequence; moreover, c-src
(cellular) was found in many species and is closely related to v-src (viral).

Avian leukosis virus, ALV, is similar to RSV, yet unlike RSV, ALV does not
contain an oncogene that leads to tumorigenesis. However, it is possible for
organisms infected with ALV to develop tumors. When sequenced, it was
discovered that within tumors, ALV provirus was integrated (by chance) next
to the host c-src. Thus, c-src was dubbed a proto-oncogene; under normal
conditions it functioned properly, but due to a mutation it become an active
oncogene. The concept of a proto-oncogene showed that genomes of
organisms have the potential to develop into oncogenes and give rise to
tumorigenesis.
The src protein is a proto-oncogene that possesses a unique
functionprovide details as to the novel feature of this enzyme and
its relevance to cancer.
Src is a non-receptor protein tyrosine kinase. Elevated c-src levels have
been attributed to tumorigenesis by promoting other signals. C-src contains
an SH2 domain, SH3 domain, and a tyrosine kinase domain. C-src is similar
to v-src of RSV. C-src is considered a proto-oncogene, as provirus mutation
next to c-src in a host leads to unregulated cell proliferation.

Chapter 4 Cellular Oncogenes

Explain the importance of Weinberg, et al.s, transfection
experiments using DNA from T24 bladder cancer and mouse 3T3
cells as DNA recipients. Explain why they were important?
Transfection is the procedure of introducing foreign DNA into a cell, often
achieved through the process of calcium phosphate coprecipitation. Mouse
3T3 fibroblast cells were treated with carcinogen 3-MC. The DNA from these
cells were then given to normal mouse fibroblasts. This result in an in vitro
formation of a focus of morphologically transformed cells. When injected
into a mouse, a tumor grew.
Gene amplification and the erbB2 oncogene/oncoprotein Gene
amplification is an increase in the number of copies of a gene normally
present in diploid genome. Increases of erbB2 gene copies is associated with
malignant breast cancer. Observed amplification of erB2/HER2 gene was
often correlated with an increased expression of its encoded protein.
Amplicon Unit of DNA amplification, 0.5 to 10 megabases long.
The use of human repeats (Alu sequences) in cloning the RAS gene H-RAS mutations underlying the appearance of the oncogene
Biochemical functioning of Ras (see next chapter as well), contrast
kinases
activation
Burkitts lymphoma and c-myc upregulation following translocation
The Ras oncoprotein is a pivotal signal transduction element:
explain why.

Ras oncoprotein operates in a very unique fashion to activate

downstream targets, describe this.
Reciprocal translocations (one type of rearrangement) are
important in cancer, a particular example being the Philadelphia
chromosome; explain the outcomes of translocations relevant to
cancer as a function of the underlying molecular biology (i.e.
regulatory versus structural).

Chapter 5 Receptor Tyrosine Kinases

Explain the unique nature of the RTKs and the reason why they are tightly
controlled?
Know and describe:
Growth factors and GFreceptors of the RTK class and their function,
in part, as
mitogen inducer pathways growth factors are naturally occurring
substances capable of stimulating cellular growth. EGFR (ErbB-1, HER1)
Ligand and cognate receptor, or receptor and cognate ligand RTK structure, dimerization (hetero and homo) and
transphosphorylation The composition and significance of the map kinase pathway The pleiotropic nature of the AKT pathway Evolutionary similarity between Src and RTK Examples of RTK important in normal biology and cancer Truncated v-erbB and Avian Myeloblastosis Virus RTK upregulation in cancer cells (in becoming oncoproteins) Endo-, exo-, para-, juxta-, auto-crine-why is autocrine considered a
double-whammy Hybrid RTK fusion proteins (Fig and Ros example) Ras as a binary switchGAP and GEF and GTP/GDP, and its two
switch regions Beta-catenin as an important transcription factor that is tightly
controlled Thematic modifications, Jak adapters, TGF-betaR heterodimer, G
protein coupled R Integrins, focal adhesions, binding to the ECM
(composition) One of the hallmarks of cancer is the need of cancer cells to remain
responsive to growth factors; how is this accomplished,
molecularly?

Chapter 6 Cell Signaling

Explain how ligand binding to RTKs transmits an activation signal to Ras, and
relay the three major signaling pathways positively effected by RasGTP.
The cancer cells co-option and genetic corruption of normal
signaling pathways in the cell Immediate early responses in cells starved of growth factors
(serum) (we may not go over this) RTK-Shc-Grb2-Sos-RasGTP Sos and its role as a GEF The distribution of SH2 and SH3 domains via evolution The consequence of RTK transphosphorylation Rass immediate targets Raf, PI3K, Ral-GEFs
Membrane tethering and its implications PI3K Responsible for attaching a phosphate group to the 3 hydroxyl of the
inositol moiety of membrane-embedded phosphatidylinositol. Attaches
phosphates to a phospholipid, rather than phosphorylating a protein
substrate, such as another kinase.
Phosphatidylinositol phosphate, PIP2, IP3 and PIP3 Phospholipase C AKT, PDPK1 and PTEN Rho and Ral-GEF pathways Jak and STATs Integrin structure and function Focal adhesions Extracellular matrix composition E-cadherin, adherens junctions, and beta catenin Wnt binding and inactivation of the GSK3beta complex G-protein coupled receptors NFkappa B, IKKB Neurofibromatosis protein 1 as a GTPase activating protein Cancer cells do not invent new signaling pathways, but co-opt and
corrupt existing onesexplain this.
Cancer is the result of the deregulation of a pathway within the cell that
leads to uncontrolled cell proliferation. A primary example of this is the Ras
to Raf to Myk to Erk pathway. The end result of this pathway can be one of
three things: chromatin rearrangement, protein synthesis, or transcription. If
Ras is not dephosphorylated, it is continuously downsignaling due to GTP
turning it on. This leads cell proliferation. Under normal circumstances, GTP
on Ras would be removed for GDP, which would cease downstream signaling.
Which signal transduction pathway is the most important for
establishment of
cancer and why in your estimation?
Ras to PI3K to PIP3 to Akt to Bad is very important for the establishment of
cancer. Akt is necessary in order to inhibit Bad, which triggers p53

apoptosis. Akt is also instrumental in angiogenesis. Continued

phosphorylation of this pathway does not allow a cell to die, and allows
clones of the cell to receive continued nutrients via blood vessel formation.

Guest speakers
Dr. Bonneau
Know and explain:
Multiple myeloma cancer of white blood cells, accumulation of plasma
cells in bone marrow.
Drug regimens; Velcade, dexamethosome and revlamidactions
Velcade is an injection based proteasome inhibitor. It blocks proteins that
would otherwise breakdown cellular complexes such as p53.
Dexamethasone is an anti-inflammatory steroid. Revlimid inhibits tumor
angiogenesis, tumor secreted cytokines, and tumor proliferation through
induction of apoptosis.
Autologous bone marrow transplantation Hematopoietic stem cells
are collected from body during a five hour procedure. Hematopoietic cells
give rise to immune cells. The cells are frozen in liquid nitrogen at -186
degrees C. A high dose of chemotherapy then begins. Stem cells are
infused back into body the next day. After about a week, patient no longer
has an immune system, putting patient prone to infections. Immune system
slowly begins to rebuild and then reaches normal levels after a few days.
CD34 marker CD34 molecule is a cluster of differentiation molecule
present on certain cells within the human body, coded for by the CD34 gene.
It mediates the attachment of stem cells to bone marrow ECM.
Osteolytic lesion An area with severe bone loss.
Dr. Bonneaus disease is multiple myeloma, a monoclonal tumor of
bone marrowwhat is the cell from which it arose, how did it, in his
case, arise, and how do we know it is monoclonal?
Multiple myeloma is a cancer of plasma cells, a type of white blood cell
responsible for producing antibodies. These cells are produced within the
bone marrow, and in multiple myeloma the cells accumulate and interfere
with the production of normal blood cells. Dr. Bonneau discovered he had
the disease after testing determined that his IgG antibody count was
extremely high. Multiple myeloma can be tested for monoclonality by
extrapolating tumor tissue and testing to see if the cells it is composed of are
not only phenotypically similar, but also contain within them the same
genetic mutation that gave rise to the tumor.

Dr. Meyers

What are the most frequent types of cancer in females and males?
Males prostate, females breast.
Describe the papilloma genome and the region responsible for
oncogenesis HPV is a DNA papillomavirus. Two primary oncoproteins are
E6 and E7. E6 is responsible for p53 inhibition and E7 is responsible for pRB
inhibition.
Types of cancers which arise from HPV infection Cervical cancer is a
common cancer resulting from HPV.
Gardasil Gardasil is a vaccine that aims to protect against HPV types 16
and 18, which are the two primary cervical cancer causing strains.
Why are, or are not, cancer rates uniform across ethnicities,
cultures/regions and the sexes?
Cancer rates are not uniform across ethnicities, cultures/regions, and the
sexes. Environment is a major factor in tumorigenesis. For example,
cultures that do not practice safe sex measures, such as the use of condoms,
have a higher chance of contracting HPV, leading to cervical cancer in
women.
18% of global cancers are of infectious origindescribe them.
Most HPV cancers arise in an epithelial junctional areawhy?
HPV requires an abrasion in the skin in order to infect someone. It prefers
the cells in the basement membrane to proliferate. In the cervix, HPV seeks
towards the transformation zone. In this area columnar cells of the
endocervix form a junction with the stratified squamous epithelium of the
exocervix. HPV is unable to bind to live tissue. Since HPV does not have the
host cell undergo lysis it spreads via the desquamating of infected cells.
HPV 16 and 18 are very virulent to humanswhy?
HPV 16 and 18 may be virulent to humans for many different reasons.
Foremost, it can be hypothesized that HPV 16 and 18 are perhaps in greater
number than other HPV strains. It is also possible that HPV 16 and 18
antibodies are less susceptible to the human immune system, allowing them
to invade and proliferate human tissue. HPV 16 and 18 also contain E6 and
E7, which are significant oncogenes when expressed as provirus within
human cells.
From the paper, what is the significance of episomal versus
integrated HPV
Expression as it relates to cancer?
Episomal HPV is HPV that has not yet integrated into a provirus within the
host cell. HPV DNA contains an E2 reading frame, which codes for E6 and E7
suppression. E6 and E7 are proteins that inhibit p53 (apoptosis) and pRB
respectively. Integration of HPV into host DNA disrupts and often abolishes

E2 expression. Thus, oncogenes E6 and E7 are continuously created, leading

the cell to form a tumor.
What is the most effective HPV disinfectant? What traditional
tabletop disinfectants dont work?
The best disinfectant was bleach. Common disinfectants such as ethanol,
OPA, and IPA were not effective against HPV. It is believed that the high
oxidation power of bleach is the reason it is so effective against HPV.